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tetrasodium;2-[5-acetamido-6-[4-[5-acetamido-6-[2-carboxylato-4,5-dihydroxy-6-[[3-hydroxy-4-(sulfonatoamino)-6,8-dioxabicyclo[3.2.1]octan-2-yl]oxy]oxan-3-yl]oxy-2-(hydroxymethyl)-4-methyloxan-3-yl]oxy-6-carboxylato-2,3-dihydroxycyclohexyl]oxy-4-hydroxy-2-(sulfooxymethyl)oxan-3-yl]oxy-3,4-dihydroxy-3,4-dihydro-2H-pyran-6-carboxylate

中文名称
——
中文别名
——
英文名称
tetrasodium;2-[5-acetamido-6-[4-[5-acetamido-6-[2-carboxylato-4,5-dihydroxy-6-[[3-hydroxy-4-(sulfonatoamino)-6,8-dioxabicyclo[3.2.1]octan-2-yl]oxy]oxan-3-yl]oxy-2-(hydroxymethyl)-4-methyloxan-3-yl]oxy-6-carboxylato-2,3-dihydroxycyclohexyl]oxy-4-hydroxy-2-(sulfooxymethyl)oxan-3-yl]oxy-3,4-dihydroxy-3,4-dihydro-2H-pyran-6-carboxylate
英文别名
——
tetrasodium;2-[5-acetamido-6-[4-[5-acetamido-6-[2-carboxylato-4,5-dihydroxy-6-[[3-hydroxy-4-(sulfonatoamino)-6,8-dioxabicyclo[3.2.1]octan-2-yl]oxy]oxan-3-yl]oxy-2-(hydroxymethyl)-4-methyloxan-3-yl]oxy-6-carboxylato-2,3-dihydroxycyclohexyl]oxy-4-hydroxy-2-(sulfooxymethyl)oxan-3-yl]oxy-3,4-dihydroxy-3,4-dihydro-2H-pyran-6-carboxylate化学式
CAS
——
化学式
C42H59N3Na4O35S2
mdl
——
分子量
1322.0
InChiKey
CIJQTPFWFXOSEO-UHFFFAOYSA-J
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    -26.5
  • 重原子数:
    86
  • 可旋转键数:
    17
  • 环数:
    7.0
  • sp3杂化的碳原子比例:
    0.83
  • 拓扑面积:
    612
  • 氢给体数:
    13
  • 氢受体数:
    36

ADMET

代谢
肝素钠主要通过肝脏的去硫化和/或解聚代谢,转化为分子量较低、生物活性大大降低的物种。活性片段的肾清除率约占给药剂量的10%,活性片段和非活性片段的总肾排泄量占剂量的40%。
Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower molecular weight species with much reduced biological potency. Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
右旋糖酐70、依诺肝素及其组合对血液凝固变量影响的研究,通过随机交叉方式在12名健康男性志愿者中进行。志愿者分别接受了500毫升静脉注射的右旋糖酐和40毫克皮下注射的依诺肝素。在24小时内分析了抗凝血酶IIa活性、抗凝血酶Xa活性、活化部分凝血活酶时间(APTT)、凝血因子VIII、血管性血友病因子(vWF)、出血时间和血细胞计数。结果显示,单独使用右旋糖酐并不影响抗凝血酶IIa活性和抗凝血酶Xa活性。在使用依诺肝素或依诺肝素与右旋糖酐组合治疗的组中,抗凝血酶IIa和抗凝血酶Xa活性的Amax、tmax、AUC0-8小时和AUC0-24小时没有差异。APTT只观察到轻微的变化,且治疗组之间无统计学意义。凝血因子VIII在三个治疗组中没有显著变化。然而,vWF在右旋糖酐组和右旋糖酐/依诺肝素组中显著降低(分别为p = 0.046和0.01),但两组之间没有差异。在给予试验物质后四小时,出血时间没有显著增加,且各个治疗组之间没有差异。这些发现表明,在使用血栓预防剂量时,右旋糖酐可以与依诺肝素联合使用,而不会增加出血风险。
The effect on hemostatic variables by dextran 70, enoxaparin and their combinations, given in doses of 500 mL i.v. and 40 mg s.c. respectively, was studied in a randomised cross-over fashion in twelve healthy male volunteers. Antifactor-IIa activity, antifactor-Xa activity, APTT, factor VIII, vWF, bleeding time and blood counts were analysed over a 24-hr period. Dextran alone did not affect antifactor-IIa activity and antifactor-Xa activity. No difference in antifactor-IIa and antifactor-Xa activity was found for Amax, tmax, AUC0-8 hr and AUC0-24 hr in the groups treated with enoxaparin or the combination of enoxaparin and dextran. Only minor changes in APTT were observed without statistical significance between the treatment groups. Factor VIII did not change significantly in the three treatment groups. However, vWF was significantly reduced in the dextran and the dextran/enoxaparin group (p = 0.046 and 0.01 respectively) but no difference was found between the two groups. Bleeding time was not significantly increased four hours after administration of the test substances and no difference was found between the individual treatment groups. /These/ findings indicate that dextran can be combined with enoxaparin, when used in thromboprophylactic doses, without increased risk for bleeding.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 解毒与急救
为了在很大程度上中和恩诺沙平过量使用的效果,鱼精蛋白硫酸盐的剂量取决于给予的低分子肝素的剂量、给药后经过的时间和血液凝固研究。如果恩诺沙平在之前的8小时内被给予,鱼精蛋白硫酸盐的剂量应等于给予的恩诺沙平钠剂量(即,1毫克的鱼精蛋白硫酸盐应被给予以中和1毫克的恩诺沙平钠)。如果恩诺沙平给药后已超过8小时,可以每给予1毫克恩诺沙平钠输注0.5毫克的鱼精蛋白硫酸盐。如果在第一次鱼精蛋白输注后2-4小时测量的活化部分凝血活酶时间(aPTT)仍然延长,可以每给予1毫克恩诺沙平钠再给予0.5毫克鱼精蛋白硫酸盐的第二个剂量。如果恩诺沙平给药后已超过12小时,可能不需要给予鱼精蛋白。然而,即使在高剂量的鱼精蛋白硫酸盐之后,aPTT可能比常规非分级肝素过量治疗后的情况更加延长,因为抗因子Xa活性永远不会被完全中和。在恩诺沙平过量使用时,鱼精蛋白硫酸盐给药可以中和大约60%的抗因子Xa活性。
To largely neutralize the effects of enoxaparin following overdosage, the dose of protamine sulfate is determined by the administered dose of the low molecular weight heparin, the time elapsed since the drug was given, and blood coagulation studies. The dose of protamine sulfate to be given should be equal to that of the administered enoxaparin sodium dose if enoxaparin was administered in the previous 8 hours (ie, 1 mg of protamine sulfate should be given to neutralize 1 mg of enoxaparin sodium). If more than 8 hours has elapsed since enoxaparin was administered, an infusion of 0.5 mg of protamine sulfate may be given for each 1 mg of enoxaparin sodium administered. If the activated partial thromboplastin time (aPTT) measured 2-4 hours after the first protamine infusion remains prolonged, a second dose of 0.5 mg of protamine sulfate may be given for each 1 mg of enoxaparin sodium administered. Protamine administration may not be required if more than 12 hours has elapsed since administration of enoxaparin. However, even after higher dosages of protamine sulfate, the aPTT may remain more prolonged than would be the case following treatment of overdosage of conventional unfractionated heparin since anti-factor Xa activity is never completely neutralized. A maximum of about 60% of anti-factor Xa activity is neutralized with protamine sulfate administration for overdosage of enoxaparin.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 解毒与急救
应特别注意避免使用硫酸鱼精蛋白过量。给予硫酸鱼精蛋白可能会导致严重的低血压和类过敏反应。因为已经有过报告称使用硫酸鱼精蛋白发生了致命反应,这些反应通常类似于过敏性反应,所以只有在复苏技术和过敏性休克治疗措施都准备好的情况下才应给予硫酸鱼精蛋白。有关更多信息,请参阅硫酸鱼精蛋白注射产品的标签。
Particular care should be taken to avoid overdosage with protamine sulfate. Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions, often resembling anaphylaxis, have been reported with protamine sulfate, it should be given only when resuscitation techniques and treatment of anaphylactic shock are readily available. For additional information consult the labeling of protamine sulfate injection products.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 解毒与急救
/SRP:/ 立即急救:确保已经进行了充分的中和。如果患者停止呼吸,请开始人工呼吸,最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩,按训练操作。如有必要,执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐,让患者向前倾或将其置于左侧(如果可能的话,头部向下),以保持呼吸道畅通,防止吸入。保持患者安静,维持正常体温。寻求医疗帮助。 /毒物A和B/
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 解毒与急救
/SRP:/ 基本治疗:建立专利气道(如有需要,使用口咽或鼻咽气道)。如有必要,进行吸痰。观察呼吸不足的迹象,如有需要,辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿,如有必要,进行治疗……。监测休克,如有必要,进行治疗……。预防癫痫发作,如有必要,进行治疗……。对于眼睛污染,立即用水冲洗眼睛。在运输过程中,用0.9%的生理盐水(NS)持续冲洗每只眼睛……。不要使用催吐剂。对于摄入,如果患者能吞咽、有强烈的干呕反射且不流口水,则用温水冲洗口腔,并给予5毫升/千克,最多200毫升的水进行稀释……。在去污后,用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
药代动力学试验是使用100毫克/毫升的制剂进行的。在皮下注射依诺肝素后3到5小时,抗凝血因子Xa和抗凝血酶(抗凝血因子IIa)的活性达到最大。在临床测试的20毫克和40毫克皮下剂量后,平均高峰抗凝血因子Xa活性分别为0.16 IU/mL(1.58 mcg/mL)和0.38 IU/mL(3.83 mcg/mL)。在不稳定型心绞痛患者中,平均(n = 46)高峰抗凝血因子Xa活性在稳态时为1.1 IU/mL,这些患者每隔12小时皮下注射1毫克/千克,持续14天。基于抗凝血因子Xa活性,健康受试者皮下注射1.5毫克/千克后,依诺肝素的平均绝对生物利用度大约为100%。
Pharmacokinetic trials were conducted using the 100 mg/mL formulation. Maximum anti-Factor Xa and anti-thrombin (anti-Factor IIa) activities occur 3 to 5 hours after SC injection of enoxaparin. Mean peak anti-Factor Xa activity was 0.16 IU/mL (1.58 mcg/mL) and 0.38 IU/mL (3.83 mcg/mL) after the 20 mg and the 40 mg clinically tested SC doses, respectively. Mean (n = 46) peak anti-Factor Xa activity was 1.1 IU/mL at steady state in patients with unstable angina receiving 1 mg/kg SC every 12 hours for 14 days. Mean absolute bioavailability of enoxaparin, after 1.5 mg/kg given SC, based on anti-Factor Xa activity is approximately 100% in healthy subjects.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
30毫克静脉注射立即随后每12小时1毫克/公斤皮下注射,提供了初始峰抗因子Xa水平为1.16 IU/mL(n=16)和平均暴露量相当于稳态水平的84%。稳态在治疗的第二天达到。
A 30 mg IV bolus immediately followed by a 1 mg/kg SC every 12 hours provided initial peak anti-Factor Xa levels of 1.16 IU/mL (n=16) and average exposure corresponding to 84% of steady-state levels. Steady state is achieved on the second day of treatment.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
依诺肝素药代动力学在推荐剂量范围内呈线性。在健康志愿者中,经过重复每日一次皮下注射40毫克和每日一次1.5毫克/公斤的方案后,稳态在第二天达到,平均暴露比单次剂量后高出约15%。稳态下的依诺肝素活性水平可以通过单次剂量药代动力学很好地预测。在重复每日两次1毫克/公斤的方案下,稳态在第4天达到,平均暴露比单次剂量后高出约65%,平均峰浓度和谷浓度分别约为1.2和0.52 IU/mL。基于依诺肝素钠的药代动力学,这种稳态差异是预期之内的,并且在治疗范围内。
Enoxaparin pharmacokinetics appear to be linear over the recommended dosage ranges. After repeated subcutaneous administration of 40 mg once daily and 1.5 mg/kg once-daily regimens in healthy volunteers, the steady state is reached on day 2 with an average exposure ratio about 15% higher than after a single dose. Steady-state enoxaparin activity levels are well predicted by single-dose pharmacokinetics. After repeated subcutaneous administration of the 1 mg/kg twice daily regimen, the steady state is reached from day 4 with mean exposure about 65% higher than after a single dose and mean peak and trough levels of about 1.2 and 0.52 IU/mL, respectively. Based on enoxaparin sodium pharmacokinetics, this difference in steady state is expected and within the therapeutic range.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
抗凝血因子Xa活性的分布容积大约为4.3升。
The volume of distribution of anti-Factor Xa activity is about 4.3 L.
来源:Hazardous Substances Data Bank (HSDB)